The risk of developing a second primary cancer after prostate cancer treatment is higher after radiation therapy compared with nonradiation therapies, investigators report.

Among 143,886 US veterans with localized prostate cancer identified using the 2000-2015 Veterans Affairs Corporate Data Warehouse, 52,886 men (36.8%) received primary radiation therapy and 91,000 (63.2%) received primary nonradiation treatments, including surgery, medical management, active surveillance, or observation. Clinicians diagnosed a second primary cancer in 1955 men (3.7%) in the radiation therapy group and 2302 men (2.5%) in the nonradiation therapy group.

Multivariable analyses showed that the risk for a second primary cancer significantly increased over time — 24%, 50%, 59%, and 47% at 0-5, 5-10, 10-15, and 15-20 years after diagnosis — in the patients who received primary radiation therapy compared with those who did not, Hilary P. Bagshaw, MD, of Stanford University in Palo Alto, California, and colleagues reported in JAMA Network Open. The number needed to harm in the radiation group decreased dramatically from 333 patients at 0-5 years to 40 patients at 20 years.

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In the radiation group, each 1-year increase in age at prostate cancer diagnosis was significantly associated with a 3% increased risk for a second primary cancer, Dr Bagshaw’s group reported. Higher Prostate Cancer Comorbidity Index scores were also associated with increased risks for a second primary cancer.

The most frequent second primary cancers included bladder cancer, leukemia, lymphoma, rectal cancer, hematoreticular cancer, soft tissue cancer, anal cancer, genital cancer, and bone cancer.

“Although the long-term toxic effects of radiotherapy are important to discuss when counseling patients on the risk-benefit profile of prostate radiotherapy, they need not deter physicians from recommending radiotherapy if appropriate,” Dr Bagshaw’s team stated. “Patient selection and shared decision-making remain important when considering prostate cancer treatment options.”

With regard to study limitations, the authors pointed out that, as with any retrospective cohort study, their data carry a risk of selection bias, “and patients treated with radiotherapy may have had more comorbid disease with a higher risk of developing a second primary cancer.” Despite adjusting for recorded comorbid disease counts using the Prostate Cancer Comorbidity Index, “it is possible that some comorbid diseases were not recorded in the patient records.” In addition, some patients in the cohort that did not receive radiotherapy may have received adjuvant or salvage radiotherapy in the years after their initial diagnosis that may not have been captured, according to the investigators.


Bagshaw HP, Arnow KD, Trickey AW, Leppert JT, Wren SM, Morris AM. Assessment of second primary cancer risk among men receiving primary radiotherapy vs surgery for the treatment of prostate cancer. JAMA Netw Open. Published online July 28, 2022. doi:10.1001/jamanetworkopen.2022.23025